Use Of Tocilizumab Research Articles

Factors influencing the length of stay in the moroccan intensive care unit in patients surviving critical COVID-19 infection

Introductionour objective is to determine the factors that influence the length of hospitalization of patients admitted to an intensive care unit. MethodsWe have conducted a mono-centric retrospective cohort of 417 patients admitted in intensive care unit for a critical infection by COVID-19, for this purpose we have realized an analytical study using the linear regression model. ResultsIn our study, the average length of hospitalization for a critical infection with COVID-19 is 6 days (SD = 7Days), regarding the factors that influence the length of hospitalization, the length of time between the consultation and the onset of symptoms higher thann 8 days affects the length of hospitalization (coefficient = 1.2 days; CI = 0.769; 2.102 and pValue = 0.009), the presence of obesity which also affects the length of hospitalization (Coefficient = 1.6 days CI ((0.009; 3.265), and pValue = 0.049). During hospitalization, the use of mechanical ventilation, the use of tocilizumab, having a billateral nosocomial pneumonia are all factors that impact the length of hospitalization. ConclusionIt is recommended to emphasize the importance of early consultation after the onset of respiratory symptoms in the patients who are admitted to the intensive care unit in order to improve the length of their stay.

Timing of Tocilizumab Administration Under the Guidance of IL-6 in CAR-T Therapy for R/R Acute Lymphoblastic Leukemia.

Chimeric antigen receptor T (CAR-T) cells targeting CD19 have achieved great clinical responses in patients with relapsed or refractory (R/R) acute B lymphoblastic leukemia. However, severe adverse events such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome restrict it to further application. Tocilizumab is the corner stone for the treatment of severe CRS. It has been used to treat mild CRS in recent years, whereas some statistical supports clarifying the suitable timing of its administration are lacking. Sixty-seven patients with B-cell acute lymphoblastic leukemia (B-ALL) were treated with CD19-CART and enrolled in the study, of which 33 patients received Tocilizumab. Application of Tocilizumab in patients with grade 2 CRS in American Society for Transplantation and Cellular Therapy (ASTCT) criteria can significantly shorten the duration of CRS without affecting side effects and long-term efficacy. However, a number of patients still developed severe CRS with early use of Tocilizumab, indicating the significance of the introduction of clinical laboratories to assist medications. Statistically, patients with less than fourfold increase in IL-6 levels had a higher incidence of severe CRS after receiving Tocilizumab (37.5% versus. 0%, p=0.0125), which provided a basis for refining CRS intervention strategies under the guidance of IL-6.Clinical Trial Registration www.clinicaltrials.gov, NCT02965092 and NCT04008251

A retrospective study of the role of Tocilizumab in preventing or controlling cytokine storm in COVID-19 cases

In spite of the advancement in science we are still lacking definite specific treatment for Covid-19. And till date (11 April 2022) 6,203,372 and 5,21,722 death occurred globally and in India respectively. The sudden increase of O2 demand with need for Invasive ventilator is an indicator/ is a warning for cytokine storm Syndrome (CSS) or an over action of the immune system, which can be disastrous. Steroids are still the best anti-inflammatory drugs available thus as soon as a patient shows signs of a 'cytokine storm,' steroids should be used. Other drugs i.e. IL-6 receptor blocker TCZ and Sarilumab and direct IL-6 inhibitor Siltuximaband JAK inhibitors (baricitinib) etc are also been considered in various trials for cytokine storm.A retrospective observational study was performed in hospitalized patients referred from the district hospital to the Dedicated Covid Hospital (DCH), all were diagnosed with COVID-19 with hypoxemia.The timely detection of CSS & early initiation to controlling management is the key issue The early identification of cytokine strom with initiation of TCZ may give beneficial result. The Oxygen requirement and CRP showed a significant decline with the use of tocilizumab. Furthermore, the optimal timing, dosage and administration route of TCZ may need to be studied with larger sample or with multicenteric study plan.

Early dexamethasone use as a protective measure in non-mechanically ventilated critically ill patients with COVID-19: a multicenter, cohort study

Dexamethasone showed mortality benefits in patients with COVID-19. However, the optimal timing for dexamethasone initiation to prevent COVID-19 consequences such as respiratory failure requiring mechanical ventilation (MV) is debatable. As a result, the purpose of this study is to assess the impact of early dexamethasone initiation in non-MV critically ill patients with COVID19. This is a multicenter cohort study including adult patients with confirmed COVID-19 admitted to intensive care units (ICUs) and received systemic dexamethasone between March 2020 and March 2021. Patients were categorized into two groups based on the timing for dexamethasone initiation (early vs. late). Patients who were initiated dexamethasone within 24 h of ICU admission were considered in the early group. The primary endpoint was developing respiratory failure that required MV; other outcomes were considered secondary. Propensity score matching (1:1 ratio) was used based on the patient’s SOFA score, MV status, prone status, and early use of tocilizumab within 24 h of ICU admission. Among 208 patients matched using propensity score, one hundred four patients received dexamethasone after 24 h of ICU admission. Among the non-mechanically ventilated patients, late use of dexamethasone was associated with higher odds of developing respiratory failure that required MV (OR [95%CI]: 2.75 [1.12, 6.76], p = 0.02). Additionally, late use was associated with longer hospital length of stay (LOS) (beta coefficient [95%CI]: 0.55 [0.22, 0.88], p = 0.001). The 30-day and in-hospital mortality were higher in the late group; however, they were not statistically significant. In non-mechanically ventilated patients, early dexamethasone use within 24 hours of ICU admission in critically ill patients with COVID-19 could be considered a proactive protective measure.

Appropriate Use of Tocilizumab in COVID-19: Early Use is Beneficial.

Interleukin-6 inhibitor Tocilizumab (TCZ) is effective to prevent the mortality of severe COVID-19 by suppressing the cytokine storm, however, its appropriate use needs to be detailed. We aimed to describe the appropriate use of TCZ in severe to critical cases with COVID-19 pneumonia in the early phase of the pandemic. This single-center, retrospective, observational study was conducted in a polymerase chain reaction (PCR) positive COVID-19 patients who received TCZ between April 01, 2020 and June 30, 2020, in Ümraniye Research and Training Hospital İstanbul, Turkey. The factors affecting mortality were compared. A total of 67 patients met the inclusion criteria during the study period. Overall, 76% of those patients were male, with a median age of 61 years. The 28-day mortality rate was 51% among all patients who were hospitalised for COVID-19 pneumonia. A logistic regression model identified the predictors of 28-day fatality; the number of comorbidities, high levels of C-reactive protein (CRP) before initiation of TCZ, initiation of TCZ in the intensive care unit (ICU) and not receiving an additional dose of TCZ. The number of comorbidities, high levels of CRP, initiation of TCZ in the ICU and not receiving the additional dose of TCZ were significant risk factors for fatality among patients with COVID-19 who received TCZ. Early initiation of TCZ when cytokine storm is suspected is appropriate for the prevention of fatality.

Real-Life Use of Tocilizumab in the Treatment of Severe COVID-19 Pneumonia.

Introduction Coronavirus disease 2019 (COVID-19) can progress to severe respiratory compromise and lead to mortality due to induction of cytokine storm. Tocilizumab (TCZ) is approved by the FDA for the treatment of cytokine release syndrome (CRS). This study aims to analyze the outcomes among patients who received TCZ in the United Arab Emirates. Methods A retrospective cohort study was conducted among COVID-19 patients who received TCZ in a tertiary care hospital from May 2020 to August 2021. For analysis, patients were divided into two groups based on survival and clinical improvement. Results Overall, 80% of patients receiving TCZ were discharged by day 28. There was a gradual improvement in oxygen requirements in our patients with a majority of them on room air by day 28. Age more than 50 years (P=0.034) and comorbidities such as cardiovascular disease (CVD) (P=0.002) and renal insufficiency (P=0.013) were significantly associated with mortality. Discussion. In our analysis, patients who were mechanically ventilated at the time of administration of TCZ had a significantly higher risk of death by day 28. In both survived and improved groups, younger patients had better outcomes than older patients. Patients who received TCZ earlier during therapy from the onset of symptoms had better survival outcomes. There was only one death among 14 patients who received vaccination. There was no significant difference in mortality among patients with comorbidities such as diabetes, hypertension, dyslipidemia, obesity, and pulmonary diseases, hypothesizing that administration of TCZ improves the outcomes in COVID-19 patients with these comorbidities.

Tocilizumab in severe COVID-19 – A randomized, double-blind, placebo-controlled trial

BackgroundThe therapeutic effectiveness of interleukin-6 receptor inhibitor in critically ill hospitalized patients with coronavirus disease 2019 (COVID-19) is uncertain. MethodsTo evaluate the efficacy and safety of the outcome as recovery or death of tocilizumab for severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection, we conducted a randomized, double-blinded, placebo-controlled phase 2 trial in critically ill COVID-19 adult patients. The patients were randomly assigned in a 4:1 ratio to receive standard medical treatment plus the recommended dose of either tocilizumab or the placebo drug. Randomization was stratified. The primary outcome was the recovery or death after administration of tocilizumab or a placebo drug. The secondary outcomes were clinical recovery or worsening of the patients' symptoms and inflammatory markers and discharge from the hospital. ResultsOf 190 patients included in this study, 152 received tocilizumab, and 38 received a placebo. The duration of hospital stay of the interventional group was 12.9 ± 9.2, while the placebo group had a more extended hospital stay (15.6 ± 8.8). The mortality ratio for the primary outcome, ie, mortality or recovery in the tocilizumab group was 17.8%; p = 0.58 by log-rank test). The mortality ratio in the placebo group was 76.3%; p = 0.32 by log-rank test). The inflammatory markers in the tocilizumab group significantly declined by day 16 compared to the placebo group. ConclusionsThe use of tocilizumab was associated with decreased mortality, earlier improvement of inflammatory markers, and reduced hospital stay in patients with severe COVID-19.

A phase 1, first-in-human (FIH) study of the anti-HER2 CAR macrophage CT-0508 in subjects with HER2 overexpressing solid tumors.

2533 Background: Most solid tumors are resistant to immunotherapy. In pre-clinical studies, CAR-M infiltrate tumors, phagocytose tumor cells, activate the tumor micro environment (TME), recruit T cells, and present tumor antigens to T cells leading to robust anti-tumor immunity. CT-0508 is a first in class CAR-M, comprised of autologous monocyte derived macrophages expressing an anti-HER2 CAR. Here we present preliminary clinical results from the CT-0508 Phase 1 FIH study. Methods: This multi-center, open-label study is evaluating CT-0508’s safety, tolerability, and manufacturing feasibility in 18 participants (pts) with advanced solid tumors overexpressing HER2 who have progressed on prior therapies. Monocytes are isolated from mobilized apheresis products, differentiated into macrophages and engineered with an anti-HER2 CAR. Group 1 pts (n = 9) receive a fractionated dose (D1, D3, D5) and Group 2 pts (n = 9) receive the full dose on D1. CT-0508 is administered without preparative chemotherapy (bridging is permitted). Serial blood samples, 1 pre and 2 post-treatment biopsies are collected to investigate safety, pharmacokinetics and mechanism of action. Results: Seven pts (4F/3M), median age 64 (49-73), have been treated [breast (2), esophageal (2), cholangiocarcinoma, ovarian and parotid gland cancers]. A median of 3 (2-10) prior lines of therapy have been administered, most pts (85.7%) received prior anti HER2 therapy. CT-0508 was successfully manufactured with high viability, purity and CAR expression, and was well tolerated with no dose limiting toxicities or AEs leading to discontinuation or dose modification. Two related SAEs were reported in the same pt (Grade 1 CRS, hospitalized for monitoring and Grade 2 infusion reaction, resolved within 1h). Three other pts had Grade 1-2 CRS; resolved within 4d with no use of tocilizumab needed. There were no major organ toxicities and no on-target off-tumor toxicities. Post-infusion cytokines were transiently elevated in most pts and were self-limiting. Among the 4 pts who reached week 8, the best overall response was stable disease (n = 3) and 1 pt progressed, with a median follow up of 8w. CT-0508 rapidly egressed from peripheral blood. CT-0508 CAR mRNA was detected in all tumor biopsies of the first 2 pts. CT-0508 activated the TME, with increased myeloid cell activation, T cell infiltration, activation and proliferation. TCR sequencing demonstrated peripherally expanding T cells enriched for tumor infiltrating lymphocyte clones, suggesting expansion of tumor reactive T cells. Correlative data from additional pts will be presented. Conclusions: In 7 pts, CT-0508 was safe and feasible to manufacture. Early correlative data demonstrate trafficking, TME modulation, and potential induction of anti-tumor T cell immunity. The study is actively enrolling. Clinical trial information: NCT04660929.

IL6-inhibitors in treatment of SARS COVID19

The aim of this study was to evaluate the clinical efficacy and safety of a two-dose approach in the administration of tocilizumab in patients with SARS COVID19
 Material and methods. The study was carried out on the basis of the Odrex Medical House in 2000-2021. The total sample included 4,112 patients hospitalized in a specialized department with coronavirus pneumonia. Of this sample, 150 patients were prescribed tocilizumab at a dose of 8 mg/kg of patient weight, including 36 (24.0 %) cases when tocilizumab was administered in a two-dose regimen. In the case of a two-dose regimen, the second dose was administered no earlier than 24 hours after the first one.
 All patients were examined according to the current clinical protocols. The hemogram, the content of CRP, ferritin, interleukin-6 were assessed. All patients received dexamethasone intramuscularly at a dose of at least 6 mg per day.
 Statistical processing was carried out by methods of analysis of variance using the software Statistica 13.0.
 Results. After the use of tocilizumab, the patients had a decrease in body temperature and a decrease in the need for oxygen support. At the same time, the normalization of indicators of the activity of the systemic inflammatory response was observed.
 Mortality after the use of tocilizumab was 29.3 %; in all cases, the deaths had an extremely severe course of coronavirus infection and a significant comorbid background. There were no manifestations of anaphylaxis and cases of secondary infection after the appointment of tocilizumab.
 Conclusions. The use of tocilizumab could significantly improve the condition of patients with SARS COVID19. There were no signs of anaphylaxis and cases of secondary infection after the administration of tocilizumab. In the absence of a pronounced clinical effect within 24 hours after the first dose of tocilizumab in patients with severe SARS COVID19, it is advisable to re-administer the drug (two-dose regimen)

Risk of Severe Infection among Rheumatoid Arthritis Patients on Biological DMARDs: A Population-Based Cohort Study.

Biological disease-modifying anti-rheumatic drugs (bDMARDs) are widely used for the management of rheumatoid arthritis, although their benefits are counterweight by an increased risk of infections. In the present study, we used administrative data to compare the risk of severe infections among different classes of bDMARDs. A retrospective cohort study was conducted using Administrative Health Databases of the Piedmont Region, Italy. Relevant data were obtained from: (1) the inhabitants registry, (2) hospital discharge records, and (3) the co-payment exemption registry and (4) drug claims registry. Fine and Gray competing risk models were fitted to evaluate the association between the use of different types of bDMARDs and occurrence of severe infection accounting for treatment interruption as competing risk. A total of 1780 new users of bDMARDs were identified. Among them, 50 hospitalizations for infection occurred during the study period. The use of Tocilizumab was associated with an increased risk of infection, compared to tumor necrosis factor (TNF) inhibitor drugs (sub-distribution hazard ratios-sHR: 2.510; 95% CI: 1.279–4.926), whereas no difference in the risk of severe infection was found for abatacept (sHR: 0.584; 95% CI: 0.234–1.457). bDMARDs treatment is generally safe in clinical practice with slight but important differences among classes. The increased risk of infection associated with tocilizumab use should be taken into account when balancing the risk and benefits of starting a treatment with this drug.

OP0185 TOCILIZUMAB IN COMBINATION WITH 8 WEEKS OF PREDNISONE FOR GIANT CELL ARTERITIS

BackgroundEven with the use of tocilizumab (TCZ), significant glucocorticoid exposure (usually ≥ 6 months) continues to be an important problem in giant cell arteritis (GCA).ObjectivesWe aimed to evaluate the efficacy and safety of tocilizumab (TCZ) in combination with 2 months of prednisone in a group of patients with GCA.MethodsWe conducted a prospective, single arm, open-label study of TCZ in combination with 2 months of prednisone for new-onset and relapsing GCA patients with active disease (ClinicalTrials.gov Identifier NCT03726749). GCA diagnosis required confirmation by temporal artery biopsy or vascular imaging. Active disease was defined as presence of cranial or polymyalgia rheumatica symptoms necessitating treatment within 6 weeks of baseline. All patients received TCZ 162 mg subcutaneously every week for 12 months and an 8-week prednisone taper starting between 20 mg and 60 mg daily (Figure 1). The primary endpoint, sustained prednisone-free remission, was defined as absence of relapse from induction of remission up to week 52 while adhering to the prednisone taper. Relapse was defined as the recurrence of symptoms of GCA requiring treatment intensification regardless of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels. Safety was also evaluated.Figure 1.Clinical Trial SchemaResultsBetween 11/2018 and 11/2020 we enrolled 30 patients (mean age 74 years, 60% females, 50% new-onset disease, 77% temporal artery biopsy-proven, 47% imaging-proven). The mean ESR and CRP at screening were 45 mm/hour and 48 mg/L, respectively. The initial prednisone dose was 60 mg (n = 7), 50 mg (n = 1), 40 mg (n = 7), 30 mg (n = 6) and 20 mg (n = 9). All patients entered remission within 4 weeks of baseline. The primary endpoint was achieved by 23 (77%) patients (Table 1). The mean (SD) cumulative prednisone dose in these 23 patients was 1052 (390) mg. After a mean period of 16 weeks, 7 (23%) patients relapsed (Table 1). All relapses but one occurred after the completion of the study prednisone taper. Overall, 6 of the 7 patients with relapse received a second prednisone taper over 8 weeks. Of these 6 patients, 4 achieved and maintained remission for the remainder of the trial period, and 2 withdrew from the study after having a second relapse. One patient with relapse received a second prednisone taper over 26 weeks and stayed in remission until the end of the study. The mean (SD) cumulative prednisone dose in the 7 patients with relapse was 1883 (699) mg (Table 1). Overall, 4 (13%) participants developed a serious adverse event (Table 1). No cases of ischemia-related visual symptoms including permanent vision loss occurred during the study.Table 1.Efficacy and Safety OutcomesGCA patients(n = 30)Efficacy Sustained, prednisone-free remission by week 5223.0 (76.7) Cumulative prednisone dose (mg) at week 52, mean (SD)1051.5 (390.3) Relapse7.0 (23.3) Time to relapse, weeks: mean (SD)15.8 (14.7) Prednisone dose (mg/day) at relapse, mean (SD)2.1 (5.2) Cumulative prednisone dose (mg), mean (SD)1883.1 (699.2) Clinical manifestations at relapse Cranial symptoms4 out of 7 patients Ischemic visual symptoms0 out of 7 patients PMR symptoms4 out of 7 patientsSafety Serious adverse events4.0 (13.3) Cellulitis1 COVID-191 Fragility fracture1 Cholecystitis1Values represent number and (%) unless otherwise specified. SD, standard deviation; PMR, polymyalgia rheumaticaConclusionThese results suggest that 12 months of TCZ in combination with 8 weeks of prednisone could be efficacious for inducing and maintaining disease remission in patients with GCA. Confirmation of these findings in a randomized controlled trial is required.Disclosure of InterestsSebastian Unizony Consultant of: Kiniksa, Sanofi, Janssen, GSK, Grant/research support from: Janssen, Genentech, Mark Matza: None declared, Adam Jarvie: None declared, Ana Fernandes: None declared, John H. Stone Consultant of: Roche/Genentech, Grant/research support from: Roche/Genentech

The safety and effectiveness of tocilizumab in older adult critically ill patients with COVID-19: a multicenter, cohort study

ObjectivesEvidence supports tocilizumab (TCZ) benefit and safety in adult patients with severe COVID-19. However, its effectiveness in critically ill older adult patients remains questionable. Thus, the study aimed to evaluate the safety and effectiveness of TCZ in older critically ill patients with COVID-19.MethodsA multicenter, retrospective study for all critically ill older adults (aged ≥65 years) with confirmed COVID-19 infection and admitted to the intensive care units (ICUs). Eligible patients were categorized into two groups based on TCZ use during ICU stay (control vs TCZ). Propensity score (PS) matching was used (1:1 ratio) based on the selected criteria. The primary outcome was the in-hospital mortality.ResultsA total of 368 critically ill older adult patients were included in the study. Fifty one patients (13.8%) received TCZ. The in-hospital mortality was lower in the TCZ group (HR 0.41; 95% CI 0.22–0.76, P-value = 0.005). Patients who received TCZ had lower odds of respiratory failure requiring mechanical ventilation (OR [95% CI]: 0.32 [0.10–0.98], P-value = 0.04). No statistically significant differences were found between the two groups for 30-days mortality, ventilator-free days, length of stay, and complications during ICU stay.ConclusionTocilizumab use in critically ill older adult patients with COVID-19 is associated with lower in-hospital mortality and a similar safety profile.

Persistent effect of tocilizumab in refractory Takayasu’s arteritis (clinical observation)

Study of the interleukin 6 (IL-6) role in chronic autoimmune inflammation has led to the development of innovative treatments for various autoimmune inflammatory rheumatic diseases, including Takayasu’s arteritis (TAK). Given the important role of IL-6 in the pathogenesis of TAK and its association with high clinical and laboratory activity of the disease, tocilizumab (TCZ) is recommended as a second-line drug if both glucocorticoids and basic antiinflammatory drugs are inefficient, and previous therapy with tumor necrosis factor-α (alpha) inhibitors. The article presents our own observation of the successful use of TCZ in a patient with refractory TAK.

The utility of CRP with the use of dexamethasone and Tocilizumab in critically ill patients with COVID-19.

The utility of CRP with the use of dexamethasone and Tocilizumab in critically ill patients with COVID-19.

Diretrizes Brasileiras para o tratamento farmacológico de pacientes hospitalizados com COVID-19

Introduction: Several therapies are being used or proposed for COVID-19, and many lack appropriate evaluations of their effectiveness and safety. The purpose of this document is to develop recommendations to support decisions regarding the pharmacological treatment of patients hospitalized with COVID-19 in Brazil. Methods: A group of 27 experts, including representatives of the Ministry of Health and methodologists, created this guideline. The method used for the rapid development of guidelines was based on the adoption and/or adaptation of existing international guidelines (GRADE ADOLOPMENT) and supported by the e-COVID-19 RecMap platform. The quality of the evidence and the preparation of the recommendations followed the GRADE method. Results: Sixteen recommendations were generated. They include strong recommendations for the use of corticosteroids in patients using supplemental oxygen, the use of anticoagulants at prophylactic doses to prevent thromboembolism and the nonuse of antibiotics in patients without suspected bacterial infection. It was not possible to make a recommendation regarding the use of tocilizumab in patients hospitalized with COVID-19 using oxygen due to uncertainties regarding the availability of and access to the drug. Strong recommendations against the use of hydroxychloroquine, convalescent plasma, colchicine, lopinavir + ritonavir and antibiotics in patients without suspected bacterial infection and also conditional recommendations against the use of casirivimab + imdevimab, ivermectin and rendesivir were made. Conclusion: To date, few therapies have proven effective in the treatment of hospitalized patients with COVID-19, and only corticosteroids and prophylaxis for thromboembolism are recommended. Several drugs were considered ineffective and should not be used to provide the best treatment according to the principles of evidence-based medicine and promote economical resource use.

MO1001: Tocilizumab in the Treatment of Chronic Antibody-Mediated Rejection Post Kidney Transplantation: Clinical and Histological Monitoring

Abstract BACKGROUND AND AIMS Chronic antibody-mediated rejection (cAMR) has very few effective therapeutic options. Interleukin-6 is an attractive target because it is involved in inflammation and humoral immunity. Therefore, the use of tocilizumab (anti-IL6 receptor, TCZ) is a potential valuable therapeutic option to treat cABMR in kidney-transplant (KT) recipients METHOD This single-centre retrospective study included all KT recipients that received monthly TCZ infusions in the setting of cABMR, between August 2018 and July 2021. We assessed 12-month renal function and KT histology during follow-up. RESULTS Forty patients were included. At 12-months, eGFR was not significantly different, 41.6 ± 17 versus 43 ± 17 mL/min/1.73 m2 (P = .102) in patients with functional graft. Six patients (15%) lost their grafts: Their condition was clinically more severe at the time of the first TCZ infusion. Histological follow-up showed no statistical difference in the scores of glomerulitis, peritubular capillaritis, and interstitial fibrosis/tubular atrophy (IFTA). However, the chronic glomerulopathy score, increased significantly over time, and conversely, arteritis and inflammation in IFTA ares improved in follow-up biopsies. CONCLUSION In our study, the addition of TCZ prevented clinical and histological worsening of cABMR in KT recipients, except for more severely ill patients. Randomized studies are needed to clarify the risk/benefit of TCZ in cABMR.

MO292: Clinical Characteristics, Management and Outcomes of Critically ill COVID-19 Patients Undergoing CRRT: Comparison Between the First Two Pandemic Waves

BACKGROUND AND AIMSAcute kidney injury (AKI) is a common complication of coronavirus disease-19 (COVID-19), which, particularly in critically ill patients requiring continuous renal replacement therapy (CRRT), is associated with an elevated mortality risk [1, 2]. However, knowledge about COVID-19 pathogenesis and management is evolving, and clinical practice is changing rapidly. Here, we evaluated if this process had an impact on the management and outcome of AKI patients.METHODSWe performed a retrospective observational study on critically ill adult COVID-19 patients who received CRRT in the intensive care unit (ICU) during the first two pandemic waves before the availability of COVID-19 vaccines: the first one from March to August 2020 (first) and the second one (second) from September to December 2020.RESULTSOverall, we considered 63 patients, aged 65 (60–69) years, 76.2% males. The main comorbidities were diabetes (DM), cardiovascular disease (CVD) and chronic kidney disease (CKD). Among them, 28 (44%) were in the first group and 35 (66%) in the second group. There were no significant differences in general characteristics, such as in comorbidities, except for a higher prevalence of CVD in the first group (Fig. 1). Lab examinations at ICU admission, including serum creatinine level (sCr), were not different between the two groups. While all patients required respiratory support, non-invasive ventilation was more prevalent in the second wave. Notably, during this period, decapneization combined with CRRT was introduced. Regarding drugs, we found that in the second group, hydroxychloroquine was abandoned, tocilizumab use was reduced and heparin administration significantly increased. The AKI time course was similar between the patients of the two waves (Fig. 2). There were no significant differences in CRRT techniques. However, in the second, the use of additional CRRT-devices, in particular adsorption-based filters, significantly increased. In most cases, citrate anticoagulation was used in both groups. Looking at the outcomes, we found no significant difference between the two waves. Indeed, 17 (60.2%) and 22 (62.8%) patients died in the ICU in the first and second groups, respectively. The length of ICU hospitalization, days on CRRT, invasive ventilation and DM were significantly related to overall mortality; time of ICU hospitalization was the only remaining significant at multivariate Cox regression. Overall, 21 (33%) patients survived hospitalization. At the 6 months after the discharge, 3 of them died, 3 were on HD and 15 were dialysis-free, even if 6 of them presented CKD.FIGURE 1:Clinical characteristics and ICU management of critically ill COVID-19 patients undergoing CRRT.FIGURE 2:Kidney function and management of critically ill COVID-19 patients undergoing CRRT.CONCLUSIONOur data confirm the high complexity and mortality of COVID-19 patients undergoing CRRT. Comparing the first two pandemic waves, we found that the patients also presented similar characteristics in terms of renal function and AKI time course. Regarding treatments, we observed some significant modifications in the management of ventilation, drug administration and dialysis membranes, mainly because of the results of ongoing clinical trials. However, these changes did not impact patients’ outcomes.These data support the view that only game-change strategies, such as vaccination or infection-specific drugs, may impact the presentation and outcome of COVID-19 patients undergoing CRRT.Finally, patients surviving this condition deserve special attention in the follow-up.

EFFICACY OF REMDESIVIR VERSUS REMDESIVIR PLUS TOCILIZUMAB IN MODERATE TO SEVERE COVID-19 PATIENTS ADMITTED IN THE CRITICAL CARE UNIT OF A TERTIARY CARE HOSPITAL IN WEST BENGAL, INDIA

Background And Aims: Severe corona virus infection is often associated with hyper immune response and liberation of inammatory cytokines. Anti-interleukin-6 receptor monoclonal antibody like tocilizumab might be effective in corona virus infection. Present study was designed to assess the effect of adding tocilizumab to remdesivir and other supportive therapy in management of critically ill covid-19 patients. Methods: This Randomized open-level clinical trial was done in 50 critically ill Covid-19 patients (from December 2020 to February 2021). They were randomly allocated in two group; to receive either injection remdesivir (Group R) or injection remdesivir plus tocilizumab (Group RT) intravenously. Patients were assessed using daily record sheets capturing data on the six-category ordinal scale and safety prole from day-1 to day28 or discharge or death. Other clinical data were recorded using the WHO International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC) case record form. Primary endpoint with respect to the efcacy of the drugs was based on proportion of patients achieving clinical improvement dened as a two point reduction in six point ordinal scale from patients admission status or live discharge from the hospital, which ever came rst. Results: Baseline characteristics were identical in both R and RT group. Biomarkers, C reactive protein, IL-6 and serum ferritin levels were signicantly more in RT group as compared to R group on day 1,3 and 7. But C reactive protein (CRP), serum ferritin and IL-6 levels from day 1 to day 7 gradually decreased in RT group and increased in R group. Conclusion: In spite of higher levels of biomarkers morbidity and mortality of patients did not increase in RT group; use of tocilizumab might be responsible for the gradual reduction in the level of biomarkers in this group.

Tocilizumab as a first-line biologic treatment in rheumatoid arthritis patients – the impact of concomitant methotrexate treatment and Rheumatic Disease Comorbidity Index on the clinical response – results from the multicenter observational ACT-POL study

ObjectivesAccording to the EULAR recommendations, remission or low disease activity (LDA) in rheumatoid arthritis should be achieved by a maximum of 6 months (M6) of treatment. Data on the use of tocilizumab (TCZ) as first-line biologic treatment in rheumatoid arthritis (RA) in routine clinical practice in Poland are lacking.Material and methodsThis multicenter, non-interventional, prospective, observational study recruited adults, presenting with moderate-to-severe RA, showing an inadequate response or intolerance to disease-modifying antirheumatic drugs, where TCZ was the first-line biologic treatment. The effectiveness of TCZ was assessed by the proportion of patients achieving remission and low disease activity following 6 months of treatment with intravenous TCZ. The impact of comorbidities on treatment outcomes was measured using the Rheumatic Disease Comorbidity Index (RDCI).ResultsTotal remission rates at months 3 and 6 were 6% and 31%, respectively. Low disease activity was reported in 10% and 92% of the patients at 3 and 6 months, respectively. The response was comparable between TCZ as monotherapy and in combination with methotrexate. Mean DAS28 decreased from 6.61 at baseline to 4.27 at the scheduled time of the assessment (3 and 6 months). The Rheumatic Disease Comorbidity Index was not correlated with the number of patients achieving LDA at M3 and M6 or remission rates at M6. Remission rates correlated with RDCI at M3. A total of 114 adverse events were reported in 61 patients, among which five were considered as serious.ConclusionsThe study confirms the effectiveness and safety of TCZ in real-world settings as a first-line biologic treatment in patients with moderate-to-severe RA. Importantly, comorbidities do not affect the results of 6-month treatment with TCZ, that is, the optimal time to achieve at least LDA. Our results may improve the effects of RA therapy in Poland, especially in patients with comorbidities and those who, for various reasons, cannot receive optimal treatment with methotrexate.

Severe Multi-inflammatory Syndrome in Children Temporally Related to COVID 19-Clinical Course, Laboratory Profile and Outcomes from a North Indian PICU.

Objective: We describe the trajectory of clinical course, laboratory markers and outcomes in children with severe multi-inflammatory syndrome temporally related to COVID-19 (MIS-C) admitted to our pediatric intensive care unit (PICU). Methods: This was a prospective case series of children admitted to PICU between May 1, 2020 and January 31, 2021, fulfilling the case definition of MIS-C published by World Health Organization (WHO) or Centers for Disease Control and Prevention (CDC). We analyzed demographic, clinical, laboratory data and echocardiographic findings. We also plotted the variation in trends between survivors and nonsurvivors. Results: Of the 34 critically ill children referred to PICU with diagnosis of MIS-C only 17 fulfilled the WHO/CDC classification of MIS-C, rest were MISC mimickers albeit other tropical infections. Median age at admission was 4 years (range 1y 6 mo-8 years). Fever, rash and conjunctival redness were most prominent symptoms. Myocardial involvement was seen in 70.5% while 76.4% developed shock; Invasive mechanical ventilation was required in 64.7% cases. Inflammatory markers showed a downward trend such as-median C- reactive protein (mg/L) had a serial reduction in levels-from (median/IQR) 210 (132.60, 246.90) at admission to 52.3 (42, 120) on Day 3. Median Ferritin (ng/ml) (n = 12) was 690 (203, 1324), serum LDH (IU/L) (n = 12) was 505 (229.5, 1032) and Mean D-dimer (ng/ml) (n = 7) was 5093.85 (1991.65), suggestive of hyperinflammatory syndrome. Twelve patients received intravenous immune globulin, with adjunctive steroid therapy used in two third of the cases. Six children died, 4 of them were under-5 years of age. Tocilizumab was prescribed in two children with high vasotrope inotrope score (VIS), cardiogenic shock and oxygenation index more than 15, both survived. Conclusions: Severe MIS-C has a heterogenous presentation, local or regional outbreaks of prevalent infectious diseases often lead to confusion and overdiagnosis. Higher proportion of mortality was seen in Under -5 children with MISC. Shock-like presentation, presence of myocardial dysfunction or nonsurvivor status is associated with higher trend of inflammatory markers and more profound multi-organ dysfunction. If disease progresses rapidly despite first line therapy (IvIg and steroids), use of Tocilizumab should be considered-as a rescue therapy under resource limitations in the absence of extracorporeal support.